4zla: Difference between revisions
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==Bestatin complex structure of leucine aminopeptidase from Helicobacter pylori== | |||
<StructureSection load='4zla' size='340' side='right'caption='[[4zla]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4zla]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Helicobacter_pylori_26695 Helicobacter pylori 26695]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZLA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZLA FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BCT:BICARBONATE+ION'>BCT</scene>, <scene name='pdbligand=BES:2-(3-AMINO-2-HYDROXY-4-PHENYL-BUTYRYLAMINO)-4-METHYL-PENTANOIC+ACID'>BES</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4zla FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zla OCA], [https://pdbe.org/4zla PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zla RCSB], [https://www.ebi.ac.uk/pdbsum/4zla PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zla ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/AMPA_HELPY AMPA_HELPY] Presumably involved in the processing and regular turnover of intracellular proteins. Catalyzes the removal of unsubstituted N-terminal amino acids from various peptides (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The M17 aminopeptidase from the carcinogenic gastric bacterium Helicobacter pylori (HpM17AP) is an important housekeeping enzyme involved in catabolism of endogenous and exogenous peptides. It is implicated in H. pylori defence against the human innate immune response and in the mechanism of metronidazole resistance. Bestatin inhibits HpM17AP and suppresses H. pylori growth. To address the structural basis of catalysis and inhibition of this enzyme, we have established its specificity towards the N-terminal amino acid of peptide substrates and determined the crystal structures of HpM17AP and its complex with bestatin. The position of the d-phenylalanine moiety of the inhibitor with respect to the active-site metal ions, bicarbonate ion and with respect to other M17 aminopeptidases suggested that this residue binds to the S1 subsite of HpM17AP. In contrast to most characterized M17 aminopeptidases, HpM17AP displays preference for L-Arg over L-Leu residues in peptide substrates. Compared to very similar homologues from other bacteria, a distinguishing feature of HpM17AP is a hydrophilic pocket at the end of the S1 subsite that is likely to accommodate the charged head group of the L-Arg residue of the substrate. The pocket is flanked by a sodium ion (not present in M17 aminopeptidases that show preference for L-Leu) and its coordinating water molecules. In addition, the structure suggests that variable loops at the entrance to, and in the middle of, the substrate-binding channel are important determinants of substrate specificity of M17 aminopeptidases. | |||
Structural basis for substrate specificity of Helicobacter pylori M17 aminopeptidase.,Modak JK, Rut W, Wijeyewickrema LC, Pike RN, Drag M, Roujeinikova A Biochimie. 2015 Nov 24. pii: S0300-9084(15)00378-8. doi:, 10.1016/j.biochi.2015.11.021. PMID:26616008<ref>PMID:26616008</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 4zla" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
==See Also== | |||
*[[Aminopeptidase 3D structures|Aminopeptidase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Helicobacter pylori 26695]] | |||
[[Category: Large Structures]] | |||
[[Category: Modak JK]] | |||
[[Category: Roujeinikova A]] | |||
Latest revision as of 11:20, 27 September 2023
Bestatin complex structure of leucine aminopeptidase from Helicobacter pyloriBestatin complex structure of leucine aminopeptidase from Helicobacter pylori
Structural highlights
FunctionAMPA_HELPY Presumably involved in the processing and regular turnover of intracellular proteins. Catalyzes the removal of unsubstituted N-terminal amino acids from various peptides (By similarity). Publication Abstract from PubMedThe M17 aminopeptidase from the carcinogenic gastric bacterium Helicobacter pylori (HpM17AP) is an important housekeeping enzyme involved in catabolism of endogenous and exogenous peptides. It is implicated in H. pylori defence against the human innate immune response and in the mechanism of metronidazole resistance. Bestatin inhibits HpM17AP and suppresses H. pylori growth. To address the structural basis of catalysis and inhibition of this enzyme, we have established its specificity towards the N-terminal amino acid of peptide substrates and determined the crystal structures of HpM17AP and its complex with bestatin. The position of the d-phenylalanine moiety of the inhibitor with respect to the active-site metal ions, bicarbonate ion and with respect to other M17 aminopeptidases suggested that this residue binds to the S1 subsite of HpM17AP. In contrast to most characterized M17 aminopeptidases, HpM17AP displays preference for L-Arg over L-Leu residues in peptide substrates. Compared to very similar homologues from other bacteria, a distinguishing feature of HpM17AP is a hydrophilic pocket at the end of the S1 subsite that is likely to accommodate the charged head group of the L-Arg residue of the substrate. The pocket is flanked by a sodium ion (not present in M17 aminopeptidases that show preference for L-Leu) and its coordinating water molecules. In addition, the structure suggests that variable loops at the entrance to, and in the middle of, the substrate-binding channel are important determinants of substrate specificity of M17 aminopeptidases. Structural basis for substrate specificity of Helicobacter pylori M17 aminopeptidase.,Modak JK, Rut W, Wijeyewickrema LC, Pike RN, Drag M, Roujeinikova A Biochimie. 2015 Nov 24. pii: S0300-9084(15)00378-8. doi:, 10.1016/j.biochi.2015.11.021. PMID:26616008[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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